ABSTRACT
BACKGROUND: Intravenous salbutamol is used to treat children with refractory status asthmaticus, however insufficient pharmacokinetic data are available to guide initial and subsequent dosing recommendations for its intravenous use. The pharmacologic activity of salbutamol resides predominantly in the (R)-enantiomer, with little or no activity and even concerns of adverse reactions attributed to the (S)-enantiomer. OBJECTIVE: Our aim was to develop a population pharmacokinetic model to characterize the pharmacokinetic profile for intravenous salbutamol in children with status asthmaticus admitted to the pediatric intensive care unit (PICU), and to use this model to study the effect of different dosing schemes with and without a loading dose. METHODS: From 19 children (median age 4.9 years [range 9 months-15.3 years], median weight 18 kg [range 7.8-70 kg]) treated with continuous intravenous salbutamol at the PICU, plasma samples for R- and S-salbutamol concentrations (111 samples), as well as asthma scores, were collected prospectively at the same time points. Possible adverse reactions and patients' clinical data (age, sex, weight, drug doses, liver and kidney function) were recorded. With these data, a population pharmacokinetic model was developed using NONMEM 7.2. After validation, the model was used for simulations to evaluate the effect of different dosing regimens with or without a loading dose. RESULTS: A two-compartment model with separate clearance for R- and S-salbutamol (16.3 L/h and 8.8 L/h, respectively) best described the data. Weight was found to be a significant covariate for clearance and volume of distribution. No other covariates were identified. Simulations showed that a loading dose can result in higher R-salbutamol concentrations in the early phase after the start of infusion therapy, preventing accumulation of S-salbutamol. CONCLUSIONS: The pharmacokinetic model of intravenous R- and S-salbutamol described the data well and showed that a loading dose should be considered in children. This model can be used to evaluate the pharmacokinetic-pharmacodynamic relationship of intravenous salbutamol in children, and, as a next step, the effectiveness and tolerability of intravenous salbutamol in children with severe asthma.
Subject(s)
Adrenergic beta-2 Receptor Agonists/pharmacokinetics , Albuterol/pharmacokinetics , Status Asthmaticus/drug therapy , Administration, Intravenous , Adolescent , Adrenergic beta-2 Receptor Agonists/administration & dosage , Adrenergic beta-2 Receptor Agonists/blood , Adrenergic beta-2 Receptor Agonists/pharmacology , Albuterol/administration & dosage , Albuterol/blood , Albuterol/pharmacology , Child , Child, Preschool , Female , Hospitalization/statistics & numerical data , Humans , Infant , Intensive Care Units, Pediatric/statistics & numerical data , Male , Models, Theoretical , Prospective Studies , Status Asthmaticus/metabolismABSTRACT
Recent literature on paediatric status asthmaticus (PSA) confirms an increasing percentage of admissions to paediatric intensive care units. PSA is a medical emergency that can be fatal and needs careful and prompt intervention. The severity of PSA is mainly determined by clinical judgement of signs and symptoms. Peak flow measurements and serial lung function measurements are not reliable in PSA. Validated clinically useful instruments are lacking. The three main factors that are involved in the pathophysiology of PSA, bronchoconstriction, mucus plugging and airway inflammation need to be addressed to optimise treatment. Initial therapies include supplementation of oxygen, repetitive administration of rapid acting ß2-agonists, inhaled anticholinergics in combination with systemic glucocorticosteroids and intravenous magnesium sulphate. Additional treatment modalities may include methylxanthines, DNase, ketamine, sodium bicarbonate, heliox, epinephrine, non-invasive respiratory support, mechanical ventilation and inhalational anaesthetics.
Subject(s)
Disease Management , Intensive Care Units, Pediatric , Status Asthmaticus/therapy , Child , HumansABSTRACT
We present the case report of a 13-month-old Caucasian toddler with symptoms of loss of consciousness, central cyanosis and uncontrolled movements of the upper limbs while taking a warm bath. The diagnosis of hot water epilepsy was supported by an ictal EEG. Hot water epilepsy, also known as bathing epilepsy or water-immersion epilepsy is, in the Caucasian population, a rare form of benign epilepsy, where seizures are provoked by immersion in a hot or even just a warm bath. This is the first comprehensive video publication of a seizure provoked by water-immersion in a Caucasian child. [Published with video sequences].
Subject(s)
Epilepsy, Reflex/physiopathology , Hot Temperature , Immersion/physiopathology , Cyanosis/etiology , Humans , Infant , Male , Unconsciousness/etiology , Videotape Recording , WaterABSTRACT
Congenital nasal pyriform aperture stenosis has been described as an unusual cause of neonatal nasal obstruction. Clinical suspicion is based on respiratory distress, cyclic cyanosis, apneas, and feeding difficulties. A bony overgrowth of the maxillary nasal processes is thought to be responsible for this deformity. This anomaly has been reported as an isolated feature or can be associated with craniofacial or central nervous system anomalies. Surgery is indicated in cases of severe respiratory distress, feeding difficulties, and when conservative methods fail.
